The present invention relates to certain aryl cyclopropyl oxime ether compounds, compositions containing these compounds, and methods for controlling fungi by the use of a fungitoxic amount of these compounds.
Compounds having certain oxime ether structures are disclosed in U.S. Pat. Nos. 5,194,662 and 5,292,759. We have discovered a group of cyclopropyl oxime ethers which possess a substituted aryl and heterocyclic moieties which possess broad spectrum fungicidal properties.
The cyclopropyloxime ethers of the present invention have the Formula (I) 
wherein X is N or CH; Z is O, S, or NR8;
A is hydrogen, halo, cyano, (C1-C12)alkyl, or (C1-C12)alkoxy;
R1 and R8 are independently hydrogen or (C1-C4)alkyl;
R2 is hydrogen, (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C2-C8)alkenyl, halo(C2-C8)alkenyl, (C2-C8)alkynyl, halo(C2-C8)alkynyl, or cyano;
R3 is hydrogen, (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C2-C8)alkenyl, halo(C2-C8)alkenyl, (C2-C8)alkynyl, or halo(C2-C8)alkynyl;
R4 and R5 are independently hydrogen, (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C2-C8)alkenyl, halo(C2-C8)alkenyl, (C2-C8)alkynyl, halo(C2-C8)alkynyl, halo, cyano, or (C1-C4)alkoxycarbonyl; and wherein
A) R7 is aryl, arylalkyl, heterocyclic or heterocyclic(C1-C4)alkyl wherein the aryl or heterocyclic ring is substituted with from 2 to 5 substituents and wherein the positions on the aryl or heterocyclic ring adjacent to the bond to the cyclopropyl ring are both substituted and R6 is hydrogen, (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C2-C8)alkenyl, halo(C2-C8)alkenyl, (C2-C8)alkynyl, or halo(C2-C8)alkynyl; or
B) R7 is aryl, arylalkyl, heterocyclic or heterocyclic(C1-C4)alkyl wherein the aryl or heterocyclic ring is unsubstituted or substituted from 1 to 4 substituents wherein at least one of the positions on the aryl or heterocyclic ring adjacent to the bond to the cyclopropyl ring is a hydrogen and R6 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C2-C8)alkenyl, halo(C2-8)alkenyl, (C2-C8)alkynyl, or halo(C2-C8)alkynyl; and their salts, complexes, enantiomorphs, and stereoisomers; and mixtures thereof.
The aforementioned (C1-C12)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl and (C3-C7)cycloalkyl groups may be optionally and independently substituted with up to three substituents selected from nitro, halomethyl, (C1-C4)alkoxycarbonyl, and cyano.
The term alkyl includes both branched and straight chain alkyl groups from 1 to 12 carbon atoms. Typical alkyl groups are methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, isooctyl, nonyl, decyl, undecyl, dodecyl and the like. The term haloalkyl refers to an alkyl group substituted with from 1 to 3 halogens.
The term alkenyl refers to an ethylenically unsaturated hydrocarbon group, straight or branched, having a chain length of from 2 to 8 carbon atoms and 1 or 2 ethylenic bonds. The term haloalkenyl refers to an alkenyl group substituted with from 1 to 3 halogen atoms. The term alkynyl refers to an unsaturated hydrocarbon group, straight or branched, having a chain length of from 2 to 8 carbon atoms and 1 or 2 acetylenic bonds.
The term aryl includes phenyl and naphthyl which maybe substituted with up to four substituents independently selected from halogen, cyano, nitro, trihalomethyl, trihalomethoxy, phenyl, phenoxy, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C2-C8)alkenyl, (C1-C4)alkoxy, (C1-C4)alkylthio, (C1-C4)alkylsulfoxide, halo(C1-C4)alkyl, halo(C1-C4)alkoxy, halo(C3-C7)cycloalkyl, halo(C2-C8)alkenyl, or (C1-C4)alkoxycarbonyl. Typical phenyl substituents, wherein at least one of the positions on the phenyl ring adjacent to the bond to the cyclopropyl ring is substituted with hydrogen include but are not limited to 2-chloro, 3-chloro, 4-chloro, 2-fluoro, 3-fluoro, 4-fluoro, 2-bromo, 3-bromo, 4-bromo, 2-methyl, 3-methyl, 4-methyl, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-methoxy, 3-methoxy, 4-methoxy, 2-trifluoromethoxy, 3-trifluoromethoxy, 4-trifluoromethoxy, 2-cyano, 3-cyano, 4-cyano, 2,3-dichloro, 2,3-difluoro, 2,3-dibromo, 2,3-dimethyl, 2,3-dimethoxy, 2,3-bis(trifluoromethyl), 2,3bis-(trifluoromethoxy), 2,4-difluoro, 2,4-dichloro, 2,4-dibromo, 2,4-dimethyl, 2,4-dimethoxy, 2,4-bis(trifluoromethyl), 2,4-bis(trifluoromethoxy), 2,5-difluoro, 2,5-dichloro, 2,5-dibromo, 2,5-dimethyl, 2,5-dimethoxy, 2,5-bis(trifluoromethyl), 2,5-bis-(trifluoromethoxy), 3,4-difluoro, 3,4-dichloro, 3,4-dibromo, 3,4-dimethyl, 3,4-dimethoxy, 3,4-bis(trifluoromethyl), 3,4-bis(trifluoromethoxy), 3,5-difluoro, 3,5-dichloro, 3,5-dibromo, 3,5-dimethyl, 3,5-bis(trifluoromethyl), 3,5-bis(trifluoromethoxy), 2,3,4-trifluoro, 2,3,4-trichloro, 2,3,4-tribromo, 2,3,4-trimethyl, 2,3,4-trimethoxy, 2,3,4-tris(trifluoromethyl), 2,3,4-tris(trifluoromethoxy), 2,3,5-trifluoro, 2,3,5-trichloro, 2,3,5-tribromo, 2,3,5-trimethyl, 2,3,5-tris(trifluoromethyl), 2,3,5-tris(trifluoromethoxy), 2,4,5-trifluoro, 2,4,5-trichloro, 2,4,5-tribromo, 2,4,5-trimethyl, 2,4,5-trimethoxy, 2,4,5-tris(trifluoromethyl), 2,4,5-tris(trifluoromethoxy), 3,4,5-trifluoro, 3,4,5-trichloro, 3,4,5-tribromo, 3,4,5-trimethyl, 3,4,5-trimethoxy, 3,4,5-tris(trifluoromethyl), 3,4,5-tris(trifluoromethoxy), 2,3,4,5-tetrafluoro, 2,3,4,5-tetrachloro, 2,3,4,5-tetrabromo, 2,3,4,5-tetramethyl, 2,3,4,5-tetramethoxy, 2,3,4,5-tetra(trifluoromethyl), and 2,3,4,5-tetra(tetrafluoromethoxy.
Typical phenyl substituents, where both positions on the phenyl ring adjacent to the bond to the cyclopropyl rings are substituted include but are not limited to 2,6-dichloro, 2,3,6-trichloro, 2,4,6-trichloro, 2,6-difluoro, 2,3,6-trifluoro, 2,4,6-trifluoro, 2,6-dibromo, 2,3,6-tribromo, 2,4,6-tribromo 2,3,4,6-tetrachloro, 2,3,5,6-tetrachloro, 2,3,4,5,6-pentachloro, 2,3,4,6-tetrabromo, 2,3,5,6-tetrabromo, 2,3,4,5,6-pentabromo, 2,3,4,6-tetrafluoro, 2,3,5,6-tetrafluoro, 2,3,4,5,6-pentafluoro, 2,6-dimethyl, 2,3,6-trimethyl, 2,4,6-trimethyl, 2,6-dimethoxy, 2,3,6-trimethoxy, 2,4,6-trimethoxy, 2,6-diethoxy, 2,3,6-triethoxy, 2,4,6-triethoxy, 2,3,4,6-tetramethyl, 2,3,5,6-tetramethyl, 2,3,4,5,6-pentamethyl, 2,3,4,6-tetramethoxy, 2,3,5,6-tetramethoxy, 2,3,4,5,6-pentamethoxy, 2,3,4,6-tetraethoxy, 2,3,5,6-tetraethoxy, 2,3,4,5,6-pentaethoxy, 2,6-dicyano, 2,3,6-tricyano, 2,4,6-tricyano, 2,6-dinitro, 2,6-diphenyl, 2,6-diphenoxy, 2,6-dibenzyl, 2,6-bis(trifluoromethyl), 2,3,6-tris(trifluoromethyl), 2,4,6-tris-(trifluoromethyl), 2,3,4,6-tetra(trifluoromethyl), 2,3,5,6-tetra(trifluoromethyl), 2,3,4,5,6-penta(trifluoromethyl), 2,6-bis-(trifluoromethoxy), 2,3,6-tris(trifluoromethoxy), 2,4,6-tris(trifluoromethoxy), 2,3,4,5-tetra(trifluoromethoxy), 2,3,4,6-tetra-(trifluoromethoxy), 2,3,5,6-tetra(trifluoromethoxy), 2,3,4,5,6-penta(trifluoromethoxy), 2-bromo-6-chloro, 2-bromo-6-fluoro, 2-bromo-6-(trifluoromethyl), 2-bromo-6-methyl, 2-bromo-6-methoxy, 2-bromo-6-(trifluoromethoxy), 2-bromo-6-cyano, 2-chloro-6-fluoro, 2-chloro-6-(trifluoromethyl), 2-chloro-6-methyl, 2-chloro-6-methoxy, 2-chloro-6-trifluoromethoxy), 2-chloro-6-cyano, 2-fluoro-6-(trifluoromethyl), 2-fluoro-6-methyl, 2-fluoro-6-methoxy, 2-fluoro-6-(trifluoromethoxy), 6-cyano-2-fluoro, 2-methyl-6-(trifluoromethyl), 6-methoxy-2-methyl, 2-methyl-6-(trifluoromethoxy), 6-cyano-2-methyl, 3,6-dichoro-2-fluoro, 3-chloro-2,6-difluoro, 4-chloro-2,6-difluoro, 2-bromo-3,6-dichoro, 2,3-dibromo-6-chloro, 3-chloro-2,6-dibromo, 2,6-dichloro-3-fluoro, 2,3-dichloro-6-fluoro, 2-chloro-3,6-difluoro, 3-bromo-2,6-dichloro, 3-bromo-2,6-fluoro, 3-bromo-6-chloro-2-fluoro, 2-bromo-5-chloro-6-fluoro, 2,6-dibromo-3-fluoro, 2,5-dibromo-6-fluoro, 2,4-dichloro-6-fluoro, 2,6-chloro-4-fluoro, 2,4,-dichloro-6-bromo, 2,6-dichloro-4-bromo, 2,4-difluoro-6-chloro, 2,4-difluoro-6-bromo, 2,6-difluoro-4-bromo, 2,4-dibromo-6-fluoro, 2,4-dibromo-6-chloro, 2,6-dibromo-4-chloro, 2,6-dibromo-4-fluoro, 2,4-dichloro-6-methyl, 2,6-dichloro-4-methyl, 2-chloro-4,6-dimethyl, 4-chloro-2,6-dimethyl, 2,4-difluoro-6-methyl, 2,6-difluoro-4-methyl, 2-fluoro-4,6-dimethyl, 4-fluoro-2,6-dimethyl, 2,4-dibromo-6-methyl, 2,6-dibromo-4-methyl, 2-bromo-4,6-dimethyl, 4-bromo-2,6-dimethyl, 2,4-dichloro-6-methoxy, 2,6-dichloro-4-methoxy, 2-chloro-4,6-dimethoxy, 4-chloro-2,6-dimethoxy, 2,4-difluoro-6-methoxy, 2,6-difluoro-4-methoxy-, 2-fluoro-4,6-dimethoxy, 4-fluoro-2,6-dimethoxy, 2,4-dibromo-6-methoxy, 2,6-dibromo-4-methoxy, 4-bromo-2,6-dimethoxy, 4-bromo-2,6-dimethoxy, 2,4-dichloro-6-(trifluoromethyl), 2,6-dichloro-4-(trifluoromethyl), 2-chloro-4,6-bis(trifluoromethyl), 4-chloro-2,6-bis(trifluoromethyl), 2,4-difluoro-6-(trifluoromethyl), 2,6-difluoro-4-(trifluoromethyl), 2-fluoro-4,6-bis(trifluoromethyl), 4-fluoro-2,6-bis(trifluoromethyl), 2,4-dibromo-6-(trifluoromethyl), 2,6-dibromo-4-(trifluoromethyl), 2-bromo-4,6-bis(trifluoromethyl), 4-bromo-2,6-bis(trifluoromethyl), 2-chloro-4,6-bis(trifluoromethoxy), 4-chloro-2,6-bis(trifluoromethoxy), 2,4-difluoro-6-(trifluoromethoxy), 2,6-difluoro-4-(trifluoromethoxy), 2-fluoro-4,6-bis(trifluoromethoxy), 4-fluoro-2,6-bis(trifluoromethoxy), 2,4-dibromo-6-(trifluoromethoxy), 2,6-dibromo-4-(trifluoromethoxy), 2-bromo-4,6-bis(trifluoromethoxy), 4-bromo-2,6-bis(trifluoromethoxy), 4,6-dichloro-2-nitro, 4,6-dibromo-2-nitro, 4,6-difluoro-2-nitro, 2,6-dichloro-4-nitro, 2-bromo-3,4,6-trichloro, 6-fluoro-2,4,5-trichloro, 6-chloro-2,4,5-tribromo, 6-fluoro-2,4,5-tribromo, 2-bromo-3,4,6-trifluoro, 2-chloro-3,4,6-trifluoro, 6-methyl-2,4,5-trichloro, 6-methyl-2,4,5-tribromo, 6-methyl-3,4,6-trifluoro, 6-(trifluoromethyl)-2,4,5-trichloro, 6-(trifluoromethyl)-2,4,5-tribromo, 2-(trifluoromethyl)-3,4,6-trifluoro, 6-(trifluoromethoxy)-2,4,5-tribromo, 2-(trifluoromethoxy)-3,4,6-trifluoro, 6-(trifluoromethoxy)-2,4,5-trichloro, 2-bromo-3,5,6-trichloro, 6-fluoro-2,3,5-trichloro, 6-chloro-2,3,5-tribromo, 6-fluoro-2,3,5-tribromo, 2-bromo-3,5,6-trifluoro, 2-chloro-3,5,6-trifluoro, 6-methyl-2,3,5-trichloro, 6-methyl-2,3,5-tribromo, 2-methyl-3,5,6-trifluoro, 6-(trifluoromethyl)-2,3,5-trichloro, 6-(trifluoromethyl)-2,3,5-tribromo, 2-(trifluoromethyl)-3,5,6-trifluoro, 2-(trifluoromethoxy)-3,5,6-trichloro, 6-(trifluoromethoxy)-2,3,5-tribromo, 2-(trifluoromethoxy)-3,5,6-trifluoro, 4-bromo-2,3,5,6-tetrachloro, 4-fluoro-2,3,5,6-tetrachloro,4-chloro-2,3,5,6-tetrabromo-, 4-fluoro-2,3,5,6-tetrabromo, 4-chloro-2,3,5,6-tetrafluoro, 4-bromo-2,3,5,6-tetrafluoro, 2-bromo-3,4,5,6-tetrachloro, 6-fluoro-2,3,4,5-tetrachloro-, 2-chloro-3,4,5,6-tetrafluoro, 2-bromo-3,4,5,6-tetrafluoro, 2-chloro-3,4,5,6-tetrabromo, 2-fluoro-3,4,5,6-tetrabromo, 4-methyl-2,3,5,6-tetrachloro, 4-methyl-2,3,5,6-tetrabromo, 4-methyl-2,3,5,6-tetrafluoro, 2,3,5,6-tetrachloro-4-(trifluoromethyl), 2,3,5,6-tetrabromo-4-(trifluoromethyl), 2,3,5,6-tetrafluoro-4-(trifluoromethyl), 2,3,5,6-tetrachloro-4-(trifluoromethoxy), 2,3,5,6-tetrabromo-4-(trifluoromethoxy, 2,3,5,6-tetrafluoro-4-(trifluoromethoxy), 6-methyl-2,3,4,5-tetrachloro, 6-methyl-2,3,4,5-tetrabromo, 2-methyl-3,4,5,6-tetrafluoro, 2,3,4,5-tetrachloro-6-(trifluoromethyl), 2,3,4,5-tetrabromo-6-(trifluoromethyl), 3,4,5,6-tetrafluoro-2-(trifluoromethyl), 2,3,4,5-tetrachloro-6-(trifluoromethoxy), 2,3,4,5-tetrabromo-6-(trifluoromethoxy), and 3,4,5,6-tetrafluoro2-(trifluoromethoxy).
The term heterocyclic refers to a substituted 6 membered unsaturated ring selected from 3- or 4-pyridinyl, 5-pyrimidinyl, 3-pyridazinyl or a 5 membered unsaturated ring selected from 3-thienyl, 3-furyl, 3-pyrrolyl, 4-isoxazolyl, 4-isothiazolyl or 4-pyrazolyl wherein both the positions on the heterocyclic ring adjacent to the bond to the cyclopropyl ring are substituted and the ring is substituted with from 2 to 4 substituents independently selected from (C1-C4) alkyl, (C3-C7)cycloalkyl, trihalomethyl, trihalomethoxy, halogen, cyano, (C1-C4)alkoxycarbonyl, nitro, phenyl, and phenoxy. The term heterocyclic also refers to a substituted or unsubstituted 6 membered unsaturated ring containing one, two or three heteroatoms, preferably one, two or three heteroatoms independently selected from oxygen, nitrogen, and sulfur or a 5 membered unsaturated ring containing one, two or three heteroatoms, preferably one or two heteroatoms independently selected from oxygen, nitrogen, and sulfur wherein the heterocyclic ring is unsubstituted or is substituted with from 1 to 3 substituents wherein at least one of the positions of the heterocyclic ring adjacent to the bond to the cyclopropyl ring is a hydrogen substituent. Examples of heterocycles include but are not limited to 2-, 3- or 4-pyridinyl, pyrazinyl, 4-, or 5-pyrimidinyl, pyridazinyl, pyrazole, imidazolyl, 2 or 3-thienyl, 2 or 3-furyl, 3-pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, and thiadiazolyl. These rings may be optionally substituted with up from 1 to 3 substituents independently selected from (C1-C4) alkyl, (C3-C7)cycloalkyl, trihalomethyl, halogen, cyano, (C1-C4)alkoxycarbonyl, nitro, phenyl, and phenoxy.
The term arylalkyl is used to describe a group wherein the alkyl chain is from 1 to 10 carbon atoms and can be branched or straight chain, preferably a straight chain, with the aryl portion, as defined above, forming a terminal portion of the arylalkyl moiety. Typical arylalkyl moieties are optionally substituted benzyl, phenethyl, phenpropyl, and phenbutyl moieties.
Typical benzyl moieties wherein at least one of the positions on the phenyl ring, adjacent to the methylene which is bonded to the cyclopropyl ring, is substituted with hydrogen include but are not limited to 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-trifluoromethylbenzyl, 3-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl 2,3-difluorobenzyl, 2,3-dichlorobenzyl, 2,3-dibromobenzyl, 2,3-dimethylbenzyl, 2,4-difluorobenzyl, 2,4-dichlorobenzyl, 2,4-dibromobenzyl, 2,4-dimethylbenzyl, 2,5-difluorobenzyl, 2,5-dichlorobenzyl, 2,5-dibromobenzyl, 2,5-dimethylbenzyl, 3,4-difluorobenzyl, 3,4-dichlorobenzyl, 3,4-dibromobenzyl, 3,4-dimethylbenzyl, 3,5-difluorobenzyl, 3,5-dichlorobenzyl, 3,5-dibromobenzyl, 3,5-dimethylbenzyl, 2,3,4-triifluorobenzyl, 2,3,4-trichlorobenzyl, 2,3,4-tribromobenzyl, and 3,4,5-trichlorobenzyl.
Typical benzyl moieties wherein both positions on the phenyl ring, adjacent to the methylene which is bonded to the cyclopropyl ring, are substituted include but are not limited to 2,6-dichlorobenzyl, 2,3,6-trichlorobenzyl, ]2,4,6-trichlorobenzyl, 2,6-difluorobenzyl, 2,3,6-fluorobenzyl, 2,4,6-trifluorobenzyl, 2,6-bis(trifluoromethyl)benzyl, 2,3,6-tris(trifluoromethyl)benzyl, 2,4,6-tris(trifluoromethyl)benzyl, 2,3,4,6-tetrachlorobenzyl, 2,3,5,6-tetrachlorobenzyl, 2,3,4,5,6-pentachlorobenzyl, 2,3,4,6-tetrabromobenzyl, 2,3,5,6-tetrabromobenzyl, 2,3,4,5,6-pentabromobenzyl, 2,3,4,6-tetrafluorobenzyl, 2,3,5,6-tetrafluorobenzyl, and 2,3,4,5,6-pentafluorobenzyl. Typical phenethyl moieties wherein at least one of the positions on the phenyl ring, adjacent to the ethyl moiety which is bonded to the cyclopropyl ring, is substituted with hydrogen include but are not limited to 2-(2-chlorophenyl)ethyl, 2-(3-chlorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(2-fluorophenyl)ethyl, 2-(3-fluorophenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(2-methylphenyl)ethyl, 2-(3-methylphenyl)ethyl, 2-(4-methylphenyl)ethyl, 2-(4-trifluoromethylphenyl)ethyl, 2-(2,4-dichlorophenyl)ethyl, and 2-(3,5-dimethoxyphenyl)ethyl. Typical phenethyl moieties wherein both positions on the phenyl ring, adjacent to the ethyl moiety which is bonded to the cyclopropyl ring, are substituted include but are not limited to 2-(2,6-dichlorophenyl)ethyl, 2-(2,3,6-trichlorophenyl)ethyl, 2-(2,4,6-trichlorophenyl)ethyl, 2-(2,6-difluorophenyl)ethyl, 2-(2,3,6-trifluorophenyl)ethyl, 2-(2,4,6-trifluorophenyl)ethyl, 2-(2,6-dimethylphenyl)ethyl, 2-(2,3,6-trimethylphenyl)ethyl, 2-(2,4,6-trimethylphenyl)ethyl, 2-(2,6-bis(trifluoromethyl)phenyl)ethyl, 2-(2,3,6-tris(trifluoromethyl)phenyl)ethyl, 2-(2,4,6-tris(trifluoromethyl)phenyl)ethyl, 2-(2,6-dimethoxyphenyl)ethyl, 2-(2,3,6-trimethoxyphenyl)ethyl, and 2-(2,4,6-trimethoxyphenyl)ethyl. Typical phenpropyl moieties wherein at least one of the positions on the phenyl ring, adjacent to the propyl moiety which is bonded to the cyclopropyl ring, is substituted with hydrogen include but are not limited to 3-phenylpropyl, 3-(2-chlorophenyl)propyl, 3-(3-chlorophenyl)propyl, 3-(4-chlorophenyl)propyl, 3-(2,4-dichlorophenyl)propyl, 3-(2-fluorophenyl)propyl, 3-(3-fluorophenyl)propyl, 3-(4-fluorophenyl)propyl, 3-(2-methylphenyl)propyl, 3-(3-methylphenyl)propyl, 3-(4-methylphenyl)propyl, 3-(4-trifluoromethylphenyl)propyl, 3-(2,4-dichlorophenyl)propyl, and 3-(3,5-dimethylphenyl)propyl. Typical phenpropyl moieties wherein both positions on the phenyl ring, adjacent to the propyl moiety which is bonded to the cyclopropyl ring, are substituted include but are not limited to 3-(2,6-dichlorophenyl)propyl, 3-(2,3,6-trichlorophenyl)propyl, 3-(2,4,6-trichlorophenyl)propyl, 3-(2,6-difluorophenyl)propyl, 3-(2,3,6-trifluorophenyl)propyl, 3-(2,4,6-trifluorophenyl)propyl, 3-(2,6-dimethylphenyl)propyl, 3-(2,3,6-trimethyl-phenyl)propyl, 3-(2,4,6-trimethylphenyl)propyl and 3-(2,6-bis(trifluoromethyl)phenyl)propyl. Typical phenbutyl moieties wherein at least one of the positions on the phenyl ring, adjacent to the butyl moiety which is bonded to the cyclopropyl ring, is substituted with hydrogen include but are not limited to 4-phenylbutyl, 4-(2-chlorophenyl)butyl, 4-(3-chlorophenyl)butyl, 4-(4-chlorophenyl)butyl, 4-(2-fluorophenyl)butyl, 4-(3-fluorophenyl)butyl, 4-(4-fluorophenyl)butyl, 4-(2-methylphenyl)butyl, 4-(3-methylphenyl)butyl, 4-(4-methylphenyl)butyl and 4-(2,4-dichlorophenyl)butyl. Typical phenbutyl moieties wherein both positions on the phenyl ring, adjacent to the butyl moiety which is bonded to the cyclopropyl ring, are substituted include but are not limited to 4-(2,6-di-chlorophenyl)butyl, 4-(2,3,6-trichlorophenyl)butyl, 4-(2,4,6-trichlorophenyl)butyl, 4-(2,6-difluorophenyl)butyl, 4-(2,3,6-trifluorophenyl)butyl, 4-(2,4,6-trifluorophenyl)butyl, 4-(2,6-dimethylphenyl)butyl, 4-(2,3,6-trimethylphenyl)butyl, 4-(2,4,6-trimethylphenyl)butyl and 4-(2,6-bis(trifluoromethyl)phenyl)butyl.
Halogen or halo includes iodo, fluoro, bromo and chloro moieties.
The compounds of the general Formula I may be obtained in preparation as E/Z isomeric mixtures. These isomers can be separated into individual components by conventional means. The substituted cyclopropanes of Formula I may be obtained in preparation as cis and trans isomeric mixtures which can be separated into individual components by conventional means. Both the individual isomeric compounds and mixtures thereof form subjects of the invention and can be used as fungicides and insecticides.
One preferred embodiment of this invention is the compounds, enantiomorphs, salts and complexes of Formula I wherein X is CH or N; Z is O or NH; A=R3=R4=R5=hydrogen; R1 and R2 are CH3; R7 is 2,6-dichlorophenyl or 2,6-difluorophenyl; and R6 is hydrogen.
Another preferred embodiment of this invention is the compounds, enantiomorphs, salts and complexes of Formula I wherein X is CH or N; Z is O or NH; A=R3=R4=R5=hydrogen; R1 and R2 are CH3; R7 is 2,6-dichlorophenyl or 2,6-difluorophenyl; and R6 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C2-C8)alkenyl, halo(C2-C8)alkenyl, (C2-C8)alkynyl, or halo(C2-C8)alkynyl.
A more preferred embodiment of this invention is the compounds, enantiomorphs, salts and complexes of Formula I wherein X is CH or N; Z is O or NH; A is hydrogen; R1 and R2 are independently (C1-C4)alkyl; R3, R4, and R5 are hydrogen; R7 is phenyl other than 2,6-dichlorophenyl or 2,6-difluorophenyl such that the positions on the phenyl ring adjacent to the bond to the cyclopropyl rings are substituted, and R6 is selected from hydrogen, (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C2-C8)alkenyl, halo(C2-C8)alkenyl, (C2-C8)alkynyl, and halo(C2-C8)alkynyl.
Another more preferred embodiment of this invention is the compounds, enantiomorphs, salts and complexes of Formula I wherein X is CH or N; Z is O or NH; A is hydrogen; R1 and R2 are independently (C1-C4)alkyl; R3, R4 and R5 are hydrogen; R6 is hydrogen or (C1-C12)alkyl; and R7 is 2,3,6-trisubstitutedphenyl, 2,4,6-trisubstitutedphenyl, 2,3,4,6-tetrasubstitutedphenyl, 2,3,5,6-tetrasubstituted, or 2,3,4,5,6-pentasubstitutedphenyl.
An even more preferred embodiment of this invention are the compounds, enantiomorphs, salts and complexes of Formula I wherein X is N; Z is NH; A is hydrogen; R1 and R2 is CH3; R3, R4 and R5 are hydrogen; R6 is hydrogen or (C1-C4)alkyl; and R7 is 2,3,6-trihalophenyl, 2,4,6-trihalophenyl, 2,3,4,6-tetrahalophenyl, 2,3,5,6-tetrahalophenyl, or 2,3,4,5,6-pentahalophenyl.
Still another preferred embodiment of this invention is the compounds, enantiomorphs, salts and complexes of in Formula I X is CH or N; Z is O or NH; A is hydrogen; R1 and R2 are independently (C1-C4)alkyl; R3, R4 and R5 are hydrogen; R7 is phenyl, phenylalkyl, or heterocyclic wherein at least one of the positions on the phenyl or heterocyclic ring adjacent to the bond to the cyclopropyl ring is a hydrogen substituent; and R6 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C2-C,)alkenyl, halo(C2-C8)alkenyl, (C2-C8)alkynyl, or halo(C2-C8)alkynyl.
Another more preferred embodiment of this invention is the compounds, enantiomorphs, salts and complexes of Formula I wherein X is N; Z is NH; A is hydrogen; R1 and R2 is (CH3); R3, R4 and R5 are hydrogen; R7 is phenyl, 2-substitutedphenyl, 3-substitutedphenyl, 4-substitutedphenyl, 2,3-disubstitutedphenyl 2,4-disubstitutedphenyl, 2,5-disubstitutedphenyl, 3,4-disubstitutedphenyl, 3,5-disubstituted, 2,3,4-trisubstitutedphenyl, 2,3,5-trisubstitutedphenyl, 2,4,5-trisubstitutedphenyl, 3,4,5-trisubstitutedphenyl, or 2,3,4,5-tetrasubstitutedphenyl; and R6is (C1-C4)alkyl or halo(C1-C4)alkyl.
A second even more preferred embodiment of this invention is the compounds, enantiomorphs, salts and complexes of Formula II wherein R7 is phenyl, 2-halophenyl, 3-halophenyl, 4-halophenyl, 2,3-dihalophenyl 2,4-dihalophenyl, 2,5-dihalophenyl, 3,4-dihalophenyl, 3,5-dihalophenyl, 2,3,4-trihalophenyl, 2,3,5-trihalophenyl, 2,4,5-trihalophenyl, 3,4,5-trihalophenyl, or 2,3,4,5-tetrahalophenyl, and R6is (C1-C4)alkyl. 
A most preferred embodiment of this invention is the compounds, enantiomorphs, salts and complexes of Formula II wherein R7 is phenyl, 2-chlorophenyl, 3-chlorophenyl, or 4-chlorophenyl, and R6 is CH3.
Typical compounds of Formula I encompassed by the present invention wherein A, R3, R4, and R5 are hydrogen; X is CH and Z is O; and R1 is methyl include those compounds presented in Table 1 of Formula III where R2, R6, and R7 are defined in Table 1. 
Table 2: Compounds 2.1 to 2.340 are compounds of Formula I wherein A, R3, R4, and R5 are hydrogen; X is N and Z is O; R1 is methyl; and R2, R6, and R7 are defined as in Table 1. Compounds 2.11 (oil) and 2.14A (oil).
Table 3: Compounds 3.1 to 3.340 are compounds of Formula I wherein A, R3, R4, and R5 are hydrogen; X is N and Z is NH, R1 is methyl; and R2, R6, and R7 are defined as in Table 1. Compounds 3.11 (oil, 4:1 A:B isomers) and 3.14A (oil, 7:3 cis:trans cyclopropane isomers).
Typical compounds of Formula I encompassed by the present invention wherein A, R3, R4, and R5 are hydrogen; X is CH and Z is O; and R1 is methyl include those compounds presented in Table 4 of Formula III where R2, R6, and R7 are defined in Table 4. 
Table 5: Compounds 5.1 to 5.158 are compounds of Formula I wherein A, R3, R4, and R5 are hydrogen; X is N and Z is O; R1 is methyl; and R2, R6, and R7 are defined as in Table 4.
Table 6: Compounds 6.1 to 6.158 are compounds of Formula I wherein A, R3, R4, and R5 are hydrogen; X is N and Z is NH, R1 is methyl; and R2, R6, and R7 are defined as in Table 4.
Typical compounds of Formula I encompassed by the present invention wherein A, R3, R4, and R5 are hydrogen; X is CH and Z is O; and R1 is methyl include those compounds presented in Table 7 of Formula III where R2, R6, and R7 are defined in Table 7 
Table 8: Compounds 8.1 to 8.231 are compounds of Formula I wherein A, R3, R4, and R5 are hydrogen; X is N and Z is O; R1 is methyl; and R2, R6, and R7 are defined as in Table 7. Compounds 8.1 (oil, 9:1 A:B isomers), 8.1A (oil), 8.1B (oil); 8.7 (oil, 7.9:2.1 A:B isomers).
Table 9: Compounds 9.1 to 9.231 are compounds of Formula I wherein A, R3, R4, and R5 are hydrogen; X is N and Z is NH, R1 is methyl; and R2, R6, and R7 are defined as in Table 7. Compounds 9.1 (oil, 9:1 A:B isomers), 9.1A (oil), 9.1B mpt 140-146xc2x0 C.; 9.7A (oil) and 9.7B (oil).
Typical compounds of Formula I encompassed by the present invention wherein A, R3, R4, and R5 are hydrogen; X is CH and Z is O; and R1 is methyl include those compounds presented in Table 10 of Formula III where R2, R6, and R7 are defined in Table 10. 
Table 11: Compounds 11.1 to 11.113 are compounds of Formula I wherein A, R3, R4, and R5 are hydrogen; X is N and Z is O; R1 is methyl; and R2, R6, and R7 are defined as in Table 7.
Table 12: Compounds 12.1 to 12.113 are compounds of Formula I wherein A, R3, R4, and R5 are hydrogen; X is N and Z is NH, R1 is methyl; and R2, R6, and R7 are defined as in Table 7.
As used in Tables 1 to 12 Ph is understood to be phenyl.
Compounds of the present invention are prepared according to the following synthetic schemes. Scheme A describes the preparation of compounds of the Formula (I) where A and R2 to R7 are as defined in Tables 1-2, 4-5, 7-8, and 10-11; X is CH or N, and Z is O (compounds of Formula VI and VII). The cyclopropyl oximes (V) are reacted with the appropriately substituted benzyl derivatives (IV), where Z is a halogen, such as bromo, chloro or iodo, preferably a benzyl bromide. A cyclopropyl substituted oxime represented by the general formula (V) is treated, at room temperature, with an appropriate base to form an anion, followed by the addition of the benzyl bromide (IV). Typical bases employed are metal hydrides such as sodium hydride, alkoxides such as sodium methoxide and hydroxide bases such as sodium or potassium hydroxide and alkali bases such as sodium or potassium carbonate. Typical solvents employed with hydride bases are N,N-dimethylformamide (DMF) and tetrahydrofuran (THF); with hydroxide bases DMF, THF, methyl ethyl ketone (MEK) and acetone and with alkali bases solvents such as DMF, acetone, and MEK.
As shown in Scheme A, the Nxe2x80x94O bond in C(R2)xe2x95x90Nxe2x80x94Oxe2x80x94, appears in the E position (assuming 
is the larger substituent). It should be recognized that the Z isomer can also be produced as well as mixtures. When isomers are produced they are designated isomer A (higher Rf on thin layer chromatography) and isomer B (lower Rf on thin layer chromatography). The determination of which isomer, A or B possesses the E or Z geometry can be made by such conventional techniques as X ray crystallography or by spectroscopic means such as nuclear magnetic resonance spectroscopy. For the compounds of the present invention isomer A has been assigned the E iminoxy configuration and isomer B, the Z iminoxy configuration. 
Compounds of formula VI (X is CH) are prepared by alkylation with methyl E-xcex1-(2-bromomethylphenyl)-xcex2-methoxyacrylate in the presence of a base, preferably NaOH or KOH, in a solvent, preferably acetone or methyl ethyl ketone. Methyl E-xcex1-(2-bromomethylphenyl)-xcex2-methoxyacrylate, as a single E isomer, can be prepared in two steps from 2-methylphenylacetate as described previously in U.S. Pat. No. 4,914,128, columns 3-4. Compounds of formula VII (X=N) are prepared by the reaction with methyl E-2-(bromomethyl)phenylglyoxylate O-methyloxime in the presence of a base, preferably NaOH or KOH, in a solvent, preferably acetone or methyl ethyl ketone. Methyl 2-(bromomethyl)phenylglyoxylate O-methyloxime can be prepared as described in U.S. Pat. No. 4,999,042, columns 17-18 and U.S. Pat. No. 5,157,144, columns 17-18. Methyl 2-(bromomethyl)phenylglyoxylate O-methyloxime is prepared from methyl 2-methylphenyl-acetate by treatment with an alkyl nitrite under basic conditions to provide after methylation, methyl 2-methyl-phenyl-glyoxalate O-methyl oxime which can also be prepared from methyl 2-methyl-phenylglyoxalate by treatment with 2-hydroxylamine hydrochloride and methylation or by treatment with methoxylamine hydrochloride. 
As shown in scheme B compounds of formula IX (X is N) and of Tables 3, 6, 9, and 12 can be prepared by the aminolysis of oximinoacetate (VII). The aminolysis of oximinoacetate to oximinoacetamides has been described in U.S. Pat. No. 5,185,342, cols. 22, 48 and 57, U.S. Pat. No. 5,221,691, cols. 26-27 and U.S. Pat. No. 5,407,902, col. 8. For example, compounds of formula VII and of Table 2 are treated with 40% aqueous methylamine in methanol to provide compounds of formula IX and of Table 3 of formula I where Z is NH. Alternatively, as is shown in scheme B intermediate unsaturated oximes (V) are reacted with N-methyl (E)-2-methoxyimino-2-[2-(bromomethyl)phenyl]acetamide VIII in the presence of a base such as an hydroxide base preferably in a solvent such as acetone or methyl ethyl ketone to provide compounds of formula (IX). N-methyl (E)-2-methoxy-imino-2-[2-(bromomethyl)phenyl]acetamide is described in U.S. Pat. No. 5,387,714, col. 13.
The oximes of the general formula (V) can be obtained, as shown in Scheme C, by reacting the corresponding cyclopropyl aldehyde or ketone (X) with hydroxylamine hydrochloride from room temperature to reflux, preferably at room temperature, in an appropriate solvent such as methanol or ethanol in the presence of an appropriate alkali such as sodium hydroxide, potassium carbonate or pyridine. A general description of the synthesis of oximes with hydroxylamine is described in March, Advanced Organic Chemistry, 4th Ed, pp. 906-907 and references therein. The oximes of the general formula (III) when obtained as a mixture of syn or anti oxime isomers can be separated into individual isomers and alkylated as described in scheme A and B. When a mixture of oximes of the general formula (III) are used in Schemes A and B the compounds of the formula VI, VII and IX can be separated into their individual isomers by conventional chromatographic techniques. 
The cyclopropyl aldehydes or ketones (X) are prepared by conventional techniques. The unsaturated intermediate XI (Scheme D) is reacted with a sulfur ylide, prepared from a dimethylsulfoxonium salt in the presence of a base, resulting in the substituted acyl cyclopropanes, X, as shown in Scheme D. The chemistry of sulfur ylides is described in Trost and Melvin, Sulfur Ylids, Academic Press, New York, N.Y. 1975 and in Block, Reactions of Organosulfur Compounds, pp. 91-123, Academic Press, New York, N.Y. 1978. Typical reaction conditions for sulfur ylide formation from a dimethylsulfoxonium salt utilizes bases such as hydroxides, metal hydrides and alkoxides in solvents such as dimethoxyethane, dimethylsulfoxide and water depending on the base employed. The reactions are conducted from 0 to 20xc2x0 C. preferably from 10-15xc2x0 C. and preferably with alkali metal hydroxides in dimethylsulfoxide. Typically dimethylsulfoxonium methylide is prepared from trimethylsulfoxonium iodide in dimethylsulfoxide in the presence of powdered sodium hydroxide at room temperature. The unsaturated aldehydes or ketones (XI) are added dropwise to the ylide and stirred at room temperature. 
The xcex1,xcex2-unsaturated aldehydes or ketones XI can be prepared by conventional condensation techniques. A extensive description of the synthesis of xcex1,xcex2-unsaturated aldehydes or ketones (enones) is described in March, Advanced Organic Chemistry, 4th Ed, pp. 937-955 and references therein. For example Organic Reactions, Volume 16 describes the general aldol condensation of ketones and aldehydes. For intermediates of formula XI of this invention, in general the ketones and aldehydes are R7COR6 (XII) and R2COCH2R3 (XIII) where R2, R3, R6, and R7 are defined previously. When R6 is hydrogen, the aldehydes R7CHO (XIV), are for example benzaldehydes (arylCHO) or heterocyclic aldehydes substituted with from 2 to 5 substituents wherein the positions on the aryl and heterocyclic ring adjacent to the bond to the cyclopropyl ring, in Formula I, are both substituted. These substituted benzaldehyes or heterocyclic aldehydes are commerically available or prepared by conventional techniques. The aldehydes R7CHO (XIV) are reacted with the ketones R2COCH2R3, XIII, (as shown in Scheme E) to provide the intermediates enones XV. Typically the ketone, R2COCH2R3, is dissolved in a hydroxylic solvent, such as methanol or ethanol, to which is added dropwise the aldehyde R7CHO followed by the base or alternatively a solution of the aldehyde in an aqueous basic solution is added. The typical bases used can be alkali metal hydroxides, such as barium, potassium or sodium hydroxide and the dropwise addition is conducted from 0xc2x0 C. to 35xc2x0 C. preferably at ambient temperature. When the enone is derived from acetone (R2 is methyl and R3 is hydrogen) the solvent can be acetone to which is added R7COR6 followed by the aqueous hydroxide solution. Preferably the aldehyde is dissolved in a solvent mixture of acetone:water (1:5) to which is added the base while stirring at room temperature. 
When R6 is not hydrogen, R7COR6 (XII) are the ketones arylCOR6 or heterocyclic ketones, substituted with from 2 to 5 substituents wherein the positions on the aryl and heterocyclic rings adjacent to the bond to the cyclopropyl ring, in Formula I, are both substituted or aryl or heterocyclic ring is unsubstituted or substituted from 1 to 4 substituents wherein at least one of the positions on the aryl or heterocyclic rings adjacent to the bond to the cyclopropyl ring, in Formula I, is a hydrogen. For the compounds of formula I where R6 is not hydrogen the intermediate unsaturated aldehydes and ketones XI are prepared, as shown in Scheme F, according to the procedures described in U.S. Pat. No. 3,950,427, col. 17 line 20, to provide after purification the E diastereiosmer (R7 is trans to R2CO in XI). In a typical preparation a ketone such as R7COR6 is reacted with an ethyl trans 3-ethoxycrotonate in dimethylformamide in the presence of potassium t-butoxide followed by acidic hydrolysis and decarboxylation to give XI. The crotonates, XVI, can be prepared from substituted ethyl acetoketones by conventional techniques 
Alternatively the xcex1,xcex2-unsaturated cyclopropyl ketones X can be prepared from cyclopropyl nitriles XIV which are prepared via cyclopropanation of the acrylonitriles XVIII as is described in Scheme G. The acrylonitriles XVIII starting materials, shown in Scheme G can be prepared by conventional synthetic methods as described in March, Advanced Organic Chemistry, 4th Ed, pp. 937-955 and references therein. For example the nitrile derivative R3CH2CN is condensed with the ketone or aldehyde R7COR6, in the presence of a base to provide the acrylonitriles XIII. Typically the a nitrile is dissolved in a solvent such as ethanol and water to which is added the aldehyde or ketone followed by a base. Typical bases used can be alkali metal hydroxides, such as barium, potassium or sodium hydroxide and the mixture is stirred typically at ambient temperature.
The acrylonitrile XVIII is treated as is described in Scheme D with a sulfur ylide to provide the cyclopropyl nitriles XVII. The cyclopropyl nitrile XVII is transformed to the cyclopropyl ketone by organometallic addition to the nitrile followed by hydrolysis. For example the standard Grignard reagents R2MgX or organolithium reagents, R2Li, add to the nitrile functionality to provide the ketone X. The addition reaction to nitriles is described in March, Advanced Organic Chemistry, 4th Ed, pp.935-936 and references cited therein. The cyclopropyl nitrile XVII can be transformed to the cyclopropyl aldehyde Xxe2x80x2 (where R2 is H) by standard reductive methods such as with diisobutylaluminum hydride (DiBAL). The formation of aldehydes from the reduction of nitrites is described in March, Advanced Organic Chemistry, 4th Ed, pp.919-920 and references cited therein. 
A direct synthesis of compounds of the formula VII or IX is shown in Scheme H. Compounds of the Formula VII or IX can be prepared directly from the functionalized cyclopropyl ketones or aldehydes, X, by condensation with the aminoxy intermediate XIX. The preparation of aminoxy intermediate XIX is described in U.S. Pat. No. 5,194,662. The aminoxy intermediate XIX is prepared in a two step sequence by the alkylation of IV (where X is N) with N-hydroxyphthalimide which is treated with hydrazine to provide XIX. The aminoxy intermediate XIX is condensed with ketones or aldehydes X to provide VII which are treated as shown in scheme B to provide IX. 
The compounds of this invention can be made according to the following procedures: